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“Exceptional” LGC paper published in Analytical and Bioanalytical Chemistry journal

29 Jul 2014
A research paper produced by a team of LGC scientists on standardisation of cell free DNA (cfDNA) measurement has been classed as “exceptional” by the Analytical and Bioanalytical Chemistry journal and selected for rapid publication.

The paper, entitled ‘Towards standardisation of cell free DNA measurement in plasma: controls for extraction efficiency, fragment size bias and quantification’ will be published in a special issue of the journal to be published in September 2014 which focuses on nucleic acid quantification.

cfDNA is detectable in circulating blood and is becoming an important clinical analyte for prenatal testing, and cancer diagnosis. For example, cfDNA in plasma or serum originating from tumours contains biomarkers which can be used for the early detection of cancer and monitoring of treatment efficacy. Also, measuring foetal DNA in maternal blood offers the potential for reducing complexity and risk associated with foetal screening methods like amniocentesis for conditions such as Down’s Syndrome.

The paper describes a study which investigated the efficiency of methods for extracting cfDNA from plasma using an in-house artificial spike-in control material along with targeting of endogenous (reference) genes to measure total cfDNA present in a sample.

Alison Devonshire, Science Leader (Nucleic Acid Metrology) and lead author of the research paper, said: “The study addresses key issues which are hindering translation of cfDNA measurement to the clinical laboratory; namely, how to control for bias due to extraction and quantification of isolated cell free DNA.”

The paper focuses on the extraction of cfDNA from plasma samples, a critical step upstream of biomarker detection and quantification, by studying differences between commercially available extraction kits tailored to this application. They also demonstrated, for the first time, how the use of multiple control (reference) genes can achieve a more reliable estimate of the total amount of cell-free DNA in a sample.

The paper was produced as part of the National Measurement System Chemical and Biological Metrology project, ‘Measurement needs for using cell free nucleic acids as diagnostic targets’, which is evaluating different purification methods and analytical techniques for detection of the foetal- or cancer-derived fraction of cfDNA.
The work also aligns with a project funded by the European Metrology Research Programme entitled ‘Traceability for biologically relevant molecules and entities’ (Bio-SI Trace), which is improving international comparability when using novel counting approaches such as digital PCR and next generation sequencing for assigning reference values and investigating impurities in biological reference materials.
On discovering that the paper had been highlighted as “exceptional” within the special issue and selected for rapid publication, Dr Devonshire said: “This recognises LGC’s leading contribution to measurement research activities that underpin tests requiring critical nucleic acid determination. Methods using cfDNA are already being applied in clinical trials; our study provides a benchmark for further development of these approaches into routine laboratory tests.”
Visit the Springer website to read the abstract and download a copy of the paper.